PUBLICATION
Peripheral positioning of lysosomes supports melanoma aggressiveness
- Authors
- Jerabkova-Roda, K., Peralta, M., Huang, K.J., Mousson, A., Bourgeat Maudru, C., Bochler, L., Busnelli, I., Karali, R., Justiniano, H., Lisii, L.M., Carl, P., Mittelheisser, V., Asokan, N., Larnicol, A., Lefebvre, O., Lachuer, H., Pichot, A., Stemmelen, T., Molitor, A., Scheid, L., Frenger, Q., Gros, F., Hirschler, A., Delalande, F., Sick, E., Carapito, R., Carapito, C., Lipsker, D., Schauer, K., Rondé, P., Hyenne, V., Goetz, J.G.
- ID
- ZDB-PUB-250410-11
- Date
- 2025
- Source
- Nature communications 16: 33753375 (Journal)
- Registered Authors
- Peralta López, Marina
- Keywords
- none
- MeSH Terms
-
- Female
- Neoplasm Invasiveness
- Zebrafish
- Lysosomes*/metabolism
- Lysosomes*/pathology
- Skin Neoplasms*/metabolism
- Skin Neoplasms*/pathology
- Cell Line, Tumor
- Animals
- Mice
- Melanoma*/genetics
- Melanoma*/metabolism
- Melanoma*/pathology
- Humans
- PubMed
- 40204688 Full text @ Nat. Commun.
Citation
Jerabkova-Roda, K., Peralta, M., Huang, K.J., Mousson, A., Bourgeat Maudru, C., Bochler, L., Busnelli, I., Karali, R., Justiniano, H., Lisii, L.M., Carl, P., Mittelheisser, V., Asokan, N., Larnicol, A., Lefebvre, O., Lachuer, H., Pichot, A., Stemmelen, T., Molitor, A., Scheid, L., Frenger, Q., Gros, F., Hirschler, A., Delalande, F., Sick, E., Carapito, R., Carapito, C., Lipsker, D., Schauer, K., Rondé, P., Hyenne, V., Goetz, J.G. (2025) Peripheral positioning of lysosomes supports melanoma aggressiveness. Nature communications. 16:33753375.
Abstract
Emerging evidence suggests that the function and position of organelles are pivotal for tumor cell dissemination. Among them, lysosomes stand out as they integrate metabolic sensing with gene regulation and secretion of proteases. Yet, how their function is linked to their position and how this controls metastasis remains elusive. Here, we analyze lysosome subcellular distribution in patient-derived melanoma cells and patient biopsies and show that lysosome spreading scales with melanoma aggressiveness. Peripheral lysosomes promote matrix degradation and cell invasion which is directly linked to the lysosomal and cell transcriptional programs. Using chemo-genetical control of lysosome positioning, we demonstrate that perinuclear clustering impairs lysosome secretion, matrix degradation and invasion. Impairing lysosome spreading significantly reduces invasive outgrowth in two in vivo models, mouse and zebrafish. Our study provides a direct demonstration that lysosome positioning controls cell invasion, illustrating the importance of organelle adaptation in carcinogenesis and suggesting its potential utility for diagnosis of metastatic melanoma.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping